Francesca Lecce

Damage to White Matter Pathways in Subacute and Chronic Spatial Neglect: A Group Study and 2 Single-Case Studies with Complete Virtual “In Vivo” Tractography Dissection

The exact anatomical localization of right hemisphere lesions that lead to left spatial neglect is still debated. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects, and lesion size may account for conflicting results that have been reported in the literature. Here, we present a comprehensive anatomical investigation of the gray- and white matter lesion correlates of left spatial neglect, which was run in a sample 58 patients with subacute or chronic vascular strokes in the territory of the right middle cerebral artery. Standard voxel-based correlates confirmed the role played by lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and temporal-parietal junction), in the frontal cortex (frontal eye field, middle and inferior frontal gyrus), and in the underlying parietal-frontal white matter. Using a new diffusion tensor imaging-based atlas of the human brain, we were able to run, for the first time, a detailed analysis of the lesion involvement of subcortical white matter pathways. The results of this analysis revealed that, among the different pathways linking parietal with frontal areas, damage to the second branch of the superior longitudinal fasciculus (SLF II) was the best predictor of left spatial neglect. The group study also revealed a subsample of patients with neglect due to focal lesion in the lateral-dorsal portion of the thalamus, which connects the premotor cortex with the inferior parietal lobule. The relevance of fronto-parietal disconnection was further supported by complete in vivo tractography dissection of white matter pathways in 2 patients, one with and the other without signs of neglect. These 2 patients were studied both in the acute phase and 1 year after stroke and were perfectly matched for age, handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken together, the results of the present study support the hypothesis that anatomical disconnections leading to a functional breakdown of parietal-frontal networks are an important pathophysiological factor leading to chronic left spatial neglect. Here, we propose that different loci of SLF disconnection on the rostro-caudal axis can also be associated with disconnection of short-range white matter pathways within the frontal or parietal areas. Such different local disconnection patterns can play a role in the important clinical variability of the neglect syndrome.

Strategy and suppression impairments after right lateral prefrontal and orbito-frontal lesions

Sir, We read with interest the scientific commentary by Hornberger and Bertoux (2015) on our study on the specificity of prefrontal cortex subregions for strategy use, verbal initiation and suppression (Robinson et al. , 2015). We administered Section 1 and 2 of the Hayling sentence completion task (Burgess and Shallice, 1997) to a large group of frontal and posterior patients. Section 1, assessing verbal initiation, requires the subject to complete sentences with an appropriate word (e.g. ‘ The captain stayed with the sinking …’ could be completed by saying ‘ ship ’). Section 2, assessing inhibition/suppression, requires the completion of sentences with an unconnected word (e.g. ‘ London is a very busy …’, could be completed by saying…‘ banana ’). This section also assesses the ability to adopt appropriate strategies. Healthy subjects are known to use heuristics in order to generate words unrelated to the sentence frame. Frontal patients may produce suppression errors (e.g. ‘ London is a very busy …’ may be completed with ‘… city ’). We found that right lateral (RL) patients were impaired on three critical variables, whereas patients with left lateral (LL) or superior medial lesions were not. Right lateral patients produced a significantly greater number of Suppression Errors, fewer Number of Correct Answers in Section 2 and had a larger Response Time difference (RTs Section 2 − RTs Section 1), a measure taken to indicate the additional ‘thinking time’ required to generate unconnected rather than appropriate words. We suggested that the right lateral region has a key role in generating or implementing an effective strategy. Other studies have previously documented that lesions in right rostral prefrontal cortex or right inferior frontal gyrus are linked to suppression impairments (Roca et al. , 2010). However, our study was the first to link these deficits to impairment …

Time-dilation and time-contraction in an anisochronous and anisometric visual scenery.

Several studies show that visual stimuli traveling at higher velocities are overestimated with respect to slower, or stationary, stimuli of equivalent physical duration. This effect-time dilation-relates more in general to several accounts highlighting a quantitative relationship between the amount of changes a stimulus is subject to and the perceived duration: faster stimuli, subject to a greater number of changes in space, lead to overestimated durations of displacement. In the present paper we provide evidence of a new illusory effect, in which the apparent duration of a sensory event is affected by the way a constant number of changes are delivered in time, or in time and space. Participants judged accelerating and decelerating sequences of stationary flickering stimuli (Experiments 1 and 3) and accelerating and decelerating horizontally drifting visual stimuli (Experiment 2) on the fronto-parallel plane. Acceleration and deceleration were achieved by irregular sequencing of events in time (anisochronous flicker rate) or irregular sequencing of events in time and space (anisochronous and/or anisometric drift). Despite being characterized by the same amounts of visual changes, accelerating and decelerating sequences lead to opposite duration biases (underestimation and overestimation errors, respectively). We refer to this effect in terms of ATI: Aniso-Time-Illusion. This bias was observed in both subsecond (760 ms) and suprasecond ranges (1900 ms). These data highlight how the spatio-temporal evolution of dynamic visual events, asides the overall quantity of changes they are subject to, affect the perceived amount of time they require to unfold.

FDG-PET/CT to predict optimal primary cytoreductive surgery in patients with advanced ovarian cancer: preliminary results.

Aims and background Primary cytoreductive surgery (CRS) has a significant impact on prognosis in epithelial ovarian cancer (EOC). Patient selection is important to recognize factors limiting optimal CRS and to avoid unnecessary aggressive surgical procedures. We evaluated the contribution of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the presurgical identification of disease sites that may preclude EOC cytoreducibility. Methods Patients with suspected EOC underwent 18F-FDG-PET/CT within 20 days before debulking surgery. The PET/CT results were compared with surgical findings and postsurgery histopathology in order to assess the diagnostic value. Results Between August 2013 and January 2014, 29 patients were evaluated. The histopathology showed 23 EOC and 6 benign tumors. The FDG-PET/CT was positive (maximum standardized uptake value [SUVmax] 11.3 ± 5.4) in 21/23 (91%) patients with EOC and provided 2 false-negatives (1 mucinous and 1 clear cell carcinoma; SUVmax ≤2.8). The FDG-PET/CT was true-negative (SUVmax 2.2 ± 1.6) in 4 out of 6 patients (67%). False-positive FDG-PET results were obtained in 2 cellular fibromas (SUVmax 4.8 and 5.6). The sensitivity, specificity, and accuracy of PET/CT to characterize ovarian masses were 91%, 67%, and 86%, respectively. Among the 21 FDG-PET/CT-positive EOC, we detected factors limiting optimal CRS in 6 cases (29%): 4 hepatic hilum infiltration and 2 root mesentery involvement, confirmed at surgical exploration. The FDG-PET did not find limiting factors in the remaining 15 patients (71%) in whom optimal CRS was obtained. Conclusions Fluorodeoxyglucose-PET/CT shows high sensitivity but suboptimal specificity in the characterization of ovarian masses. However, PET/CT may play a role in noninvasively selecting patients with EOC who can benefit from primary CRS.

Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis

OBJECTIVE We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. METHODS On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. RESULTS Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. CONCLUSIONS In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested.

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

OBJECTIVE Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. METHODS Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. CONCLUSIONS Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted.

Cingulate neglect in humans: Disruption of contralesional reward learning in right brain damage

Motivational valence plays a key role in orienting spatial attention. Nonetheless, clinical documentation and understanding of motivationally based deficits of spatial orienting in the human is limited. Here in a series of one group-study and two single-case studies, we have examined right brain damaged patients (RBD) with and without left spatial neglect in a spatial reward-learning task, in which the motivational valence of the left contralesional and the right ipsilesional space was contrasted. In each trial two visual boxes were presented, one to the left and one to the right of central fixation. In one session monetary rewards were released more frequently in the box on the left side (75% of trials) whereas in another session they were released more frequently on the right side. In each trial patients were required to: 1) point to each one of the two boxes; 2) choose one of the boxes for obtaining monetary reward; 3) report explicitly the position of reward and whether this position matched or not the original choice. Despite defective spontaneous allocation of attention toward the contralesional space, RBD patients with left spatial neglect showed preserved contralesional reward learning, i.e., comparable to ipsilesional learning and to reward learning displayed by patients without neglect. A notable exception in the group of neglect patients was L.R., who showed no sign of contralesional reward learning in a series of 120 consecutive trials despite being able of reaching learning criterion in only 20 trials in the ipsilesional space. L.R. suffered a cortical-subcortical brain damage affecting the anterior components of the parietal-frontal attentional network and, compared with all other neglect and non-neglect patients, had additional lesion involvement of the medial anterior cingulate cortex (ACC) and of the adjacent sectors of the corpus callosum. In contrast to his lateralized motivational learning deficit, L.R. had no lateral bias in the early phases of attentional processing as he suffered no contralesional visual or auditory extinction on double simultaneous tachistoscopic and dichotic stimulation and detected, with no exception, single contralesional visual and auditory stimuli. In a separate study, we were able to compare L.R. with another RBD patient, G.P., who had a selective lesion in the right ACC, in the adjacent callosal connections and the medial-basal prefrontal cortex. G.P. had no contralesional neglect and displayed normal reward learning both in the left and right side of space. These findings show that contralesional reward learning is generally preserved in RBD patients with left spatial neglect and that this can be exploited in rehabilitation protocols. Contralesional reward learning is severely disrupted in neglect patients when an additional lesion of the ACC is present: however, as demonstrated by the comparison between L.R. and G.P. cases, selective unilateral lesion of the right ACC does not produce motivational neglect for the contralesional space.

Endometrioma-associated infertility: is surgery still the best way to go?

Purpose Endometriomas are frequently associated with female infertility. In these cases, management options include surgery and IVF. The purpose of the present review is to evaluate current literature on the treatment of endometrioma-associated infertility and to compare the pros and cons of the different therapeutic approaches. Methods Literature search of published studies on the treatment of ovarian endometriomas in infertile patients. Studies were evaluated both on the efficacy of the surgical treatment on postoperative reproductive outcome and on the effect of surgery on the ovarian reserve. Results Pregnancy rates around 50% have been consistently reported after surgery, which compare favorably with those obtained with IVF. Surgery is effective also on associated pain, and the histological evaluation of the excised specimen rules out a possible unexpected ovarian malignancy. Thorough histological analysis of the excised specimen permits the evaluation of the appropriateness of surgery. Conclusions Laparoscopic excision of the ovarian endometrioma in infertile patients should still be considered the treatment of choice, particularly in case of associated pain. Surgery should be performed following appropriate techniques, and by dedicated surgeons, in order to decrease the possible damage to the ovarian reserve that has been recently reported postoperatively.

Thrombotic thrombocytopenic purpura during pregnancy versus imitator of preeclampsia.

Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organs due to a systemic endothelial cell injury secondary to a deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity. TTP is a rare complication of pregnancy with a poor prognosis and high fetal mortality, especially when it occurs during the first trimester. Recent data have supported that effective treatment of TTP is plasma therapy. Unfortunately a major problem remains in the delay in diagnosis due to confounding factors between other “imitators of preeclampsia.” Rapid and readily available laboratory testing to quickly diagnose TTP is desperately needed to improve care and to save mother and future child life.

Laparotomic myomectomy in the 16th week of pregnancy: a case report.

Myomectomy is rarely performed during an ongoing pregnancy because of fear of miscarriage and the risk of an uncontrolled haemorrhage necessitating a hysterectomy. In cases where myomectomy is undertaken, most are performed at the time of cesarean section or with a laparoscopic approach. We report a case of a successful laparotomic myomectomy in the 16th week of pregnancy. A 35-year-old primigravida was admitted to our department with acute abdominal pain and hydronephrosis (serum creatinine 1.6 mg/dL). Imaging revealed a large implant myoma compressing the bladder, ureters, rectus, and gestational chamber and causing hydronephrosis. Laparotomic myomectomy was successfully performed and pregnancy continued uneventfully until the 38th week when a cesarean section was performed. Surgical management of myomas during pregnancy is worth evaluating in well-selected and highly symptomatic cases.